The Open Leukemia Journal

2011, 4 : 1-8
Published online 2011 March 9. DOI: 10.2174/1876816401104010001
Publisher ID: TOLEUKEMIAJ-4-1

RESEARCH ARTICLE
Establishment of an Adult T-Cell Leukemia Cell Line (HU-ATTAK) Dependent for Proliferation on Human Umbilical Cord Vein Endothelial Cells

Yoshitoyo Kagami, *,1,5 , Karnan Sivasundaram3 , Aya nakagawa3 , Kazuiku Oshiro4 , Harumi Kato3 , Koichi Koike2 , Yasuo Morishima1 and Masao Seto, *,3,6
1 Department of Hematology and Cell Therapy,
2 Department of Clinical Laboratories, Aichi Cancer Center Hospital,
3 Division of Molecular Medicine, Aichi Cancer Center Research Institute,
4 Department of Hematology, Okinawa Prefectural Nanbu Medical Center & Children’s Medical Center,
5 Department of Hematology, Toyota Kosei Hospital
6 Department of Cancer Genetics, Nagoya University Graduate School of Medicine, Japan

*Address correspondence to these authors at the (YK) Department of Hematology, Toyota Kosei Hospital, 500-1, Ibohara, Josui-cho, Toyota, 470-0396, Japan; Tel: (+81) - 565-43-5000; Fax: (+81) - 565-43-5100; E-mail: and (MA) Division of Molecular Medicine, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan; Tel: (+81)-52-762-6111; Fax: (+81)-52-763-5233; E-mail: y-kagami@toyota.jaaikosei.or.jp

ABSTRACT

A novel cell line, HU-ATTAK, was established from the peripheral blood of a patient with adult T-cell leukemia by means of co-culture with human umbilical cord vein endothelial cells (HUVEC) in the presence of interleukin-2 and damnacanthal. Immunophenotypic and cytogenetic analyses showed that HU-ATTAK is originally derived from leukemic cells and maintains the typical features of adult T-cell leukemia-lymphoma (ATLL). The growth of HU-ATTAK depends on IL-2 and HUVEC. When IL-2 was removed from the culture, HU-ATTAK stopped growing and eventually died through apoptosis. On the other hand, when HUVEC was removed from the culture, HU-ATTAK ceased proliferation but survived for a period of over two weeks. A culture experiment using micropore membranes showed that attachment of HU-ATTAK to HUVEC is necessary for proliferation. Stimulation of the co-stimulatory molecule OX40 ligand, which is expressed on HUVEC, is also involved in HU-ATTAK growth because the anti-OX40 ligand antibody completely inhibited the growth. These findings suggest the importance of the microenvironment for the survival and proliferation of some cases of ATLL. The HU-ATTAK cell line may thus be useful for studying the growth mechanism of ATLL and might yield new insights into the pathogenesis of ATLL.

Keywords:

Adult T-cell leukemia/lymphoma, Human umbilical cord vein endothelial cells, OX40, cell line.